An interventional study of Very low carbohydrate ketogenic diet and Mediterranean diet in Aging and Musculoskeletal Diseases, sponsored by University of Florida. Completed at 1 site in United States. Open to participants aged 55 Years to 80 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-01-28.
Sponsored by University of Florida · Not applicable, Interventional, and Basic science
Preclinical data indicate that very low carbohydrate ketogenic diets (KD) may prevent progression of age-related sarcopenia (skeletal muscle decline) but also may disturb bone metabolism. The investigators will pilot test a randomized trial comparing the effects of short-term adaptation to a well-formulated ketogenic diet and Mediterranean diet on markers of bone metabolism and muscle function in older adults. The expected results will help inform the benefit-risk assessment for older patients considering longer term use of KD therapy.
Eucaloric very low carbohydrate ketogenic diets (KD) are therapeutic diets that mimic fasting by generating ketones for metabolic fuel while meeting nutritional requirements (nutritional ketosis). Nutritional ketosis may broadly benefit healthspan through mechanisms such as suppression of inflammation or induction of autophagy, and preclinical and emerging clinical data indicate that KD therapy may help slow progression of age-related conditions including sarcopenia. However, questions remain about the benefits and risks of KD, especially relative to recommended therapeutic diets such as the Mediterranean Diet (MD) for which there is evidence of benefit for age-related conditions. For example, KD has shown efficacy for weight loss, which could reduce ectopic lipid accumulation that weakens muscle and bone. KD has been shown to increase skeletal muscle mitochondrial mass, mitochondrial activity, and strength in aged mice, possibly by increasing peroxisome proliferator-activated receptor activity and preserving fast-oxidative fibers that typically decline with age. However, long term use of KD may adversely impact bone. KD can cause deterioration of bone in juvenile mice without evidence of undernutrition and is associated with skeletal demineralization in children being treated for drug-resistant epilepsy.
Given the burden of musculoskeletal disease in older Americans, it is vital to understand the effects of KD on the musculoskeletal system of older adults to inform the benefit-risk assessment for an older patient and to optimize the effectiveness of KD for age-related conditions. The investigators are conducting a pilot test of a randomized clinical trial comparing the effects of short-term adaptation to a well-formulated KD and MD on markers of bone health and muscle function in older adults. The investigators will supply fresh prepared meals to achieve high adherence to the dietary interventions and adequate contrast in metabolic state between treatment groups.
Potential participants will complete a screening process so the investigators can determine whether potential participants are eligible to enroll in the study. At the first screening visit, the study team will measure blood pressure, height, and weight. Individuals will complete questionnaires that collect information about their health history, dietary intake, and physical activity habits. No more than 50 mL of blood will be collected from potential participants to run routine clinical lab tests to evaluate health status.
If an individual remains eligible after the first screening visit, they will be invited to complete a 24-hour urine collection (at home) and to schedule a second screening visit. At the second screening visit, a physician will conduct a physical exam and assess their body composition with an x-ray technology called dual-energy x-ray absorptiometry (DEXA or DXA).
If an individual remains eligible after the second screening visit, they will be invited to enroll in the dietary intervention study. Once enrolled, the participant will be assigned to either a very low carbohydrate ketogenic dietary pattern or a Mediterranean dietary pattern. The investigators will provide most of the food the participant will need each day in the form of a nutrition shake (breakfast) and two prepared meals (lunch and dinner). A study dietitian will be available to provide continuous support through a secure messaging app.
While in the dietary intervention phase of the study, participants will come to the UF Clinical and Translational Science Building once a week for 6 weeks. The study team will measure participant blood pressure and weight at each visit. At the first, middle, and final visits, the study team will collect a blood sample and urine sample from participants for lab testing, and participants will complete a short series of tests that measure physical performance.
Our ultimate research goal is to determine the effects of KD on body composition and clinically relevant measures of bone health and muscle function, as those data are needed to (1) inform the benefit-risk assessment for an older patient who is considering longer term adherence to KD therapy and (2) optimize the effectiveness of KD for age-related conditions.
657 studies on the registry are indexed under Musculoskeletal Diseases; 160 are open to participants now.
This study's enrollment of 12 is below the median of 73 across 438 interventional studies indexed under Musculoskeletal Diseases.
Browse Musculoskeletal Diseases studies →University of Florida is the lead sponsor of 1,254 studies on the registry; 201 are open to participants now.
Of its 170 completed or terminated interventional studies of FDA-regulated products, 136 (80%) have results posted.
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Exclusion Criteria:
Other: Very low carbohydrate ketogenic diet
Other: Mediterranean diet
Very low carbohydrate ketogenic diet provided for six weeks
Mediterranean diet provided for six weeks
Rate of enrollment
Number of participants enrolled in dietary intervention phase per month
Time frame: Monthly. Up to 24 months.
Screen failure rate (percentage)
Number of participants deemed ineligible / number of participants screened \* 100
Time frame: Monthly. Up to 24 months.
Treatment-specific retention rates
Percentage of participants enrolled in dietary intervention phase who complete at least 6 intervention study visits including baseline, middle, and final visit.
Time frame: Either after the endline visit or when participant is withdrawn or withdraws from study
Treatment-specific adherence rates
Treatment-specific adherence rates to protocol as evidenced by (1) dietary intake (2) blood ketone concentrations
Time frame: Either after the endline visit or when participant is withdrawn or withdraws from study
Bone turnover markers
Serum CTX, urine NTX, serum TRACP-5b, serum P1NP, serum BSAP, serum osteocalcin
Time frame: Pre-intervention; during the intervention (at 3 and 6 weeks into the intervention)
Body fat percentage
Body Fat Percentage measured by dual-energy x-ray absorptiometry
Time frame: Pre-intervention; during the intervention (at 6 weeks into the intervention)
Fat mass index
Fat Mass Index measured by dual-energy x-ray absorptiometry
Time frame: Pre-intervention; during the intervention (at 6 weeks into the intervention)
Visceral Adipose Tissue
Visceral Adipose Tissue (VAT) measured by dual-energy x-ray absorptiometry
Time frame: Pre-intervention; during the intervention (at 6 weeks into the intervention)
Fat Free Mass Index
Fat Free Mass Index measured by dual-energy x-ray absorptiometry
Time frame: Pre-intervention; during the intervention (at 6 weeks into the intervention)
Skeletal Muscle Mass
Skeletal Muscle Mass measured by dual-energy x-ray absorptiometry
Time frame: Pre-intervention; during the intervention (at 6 weeks into the intervention)
Appendicular Lean Mass to Height Ratio
Appendicular Lean Mass to Height Ratio measured by dual-energy x-ray absorptiometry
Time frame: Pre-intervention; during the intervention (at 6 weeks into the intervention)
Predicted resting metabolic rate
Resting Metabolic Rate estimated from dual-energy x-ray absorptiometry data
Time frame: Pre-intervention; during the intervention (at 6 weeks into the intervention)
24-hour urine analytes
A standardized report from 24-hour urine studies
Time frame: Pre-intervention; during the intervention (at 3 and 6 weeks into the intervention)
Handgrip strength
Handgrip strength measured by dynamometer
Time frame: Pre-intervention; during the intervention (at 3 and 6 weeks into the intervention)
Total balance test score
Results of balance tests performed as part of the short physical performance battery
Time frame: Pre-intervention; during the intervention (at 3 and 6 weeks into the intervention)
Gait speed test score
Results of gait speed tests performed as part of the short physical performance battery
Time frame: Pre-intervention; during the intervention (at 3 and 6 weeks into the intervention)
Chair stand test score
Results of chair stand tests performed as part of the short physical performance battery
Time frame: Pre-intervention; during the intervention (at 3 and 6 weeks into the intervention)
Circadian clock gene expression
Relative expression of circadian genes in whole blood collected in PAXgene blood RNA tubes
Time frame: Pre-intervention; during the intervention (at 6 weeks into the intervention)
Vitamin D status
Circulating concentrations of vitamin D metabolites
Time frame: Pre-intervention; during the intervention (at 3 and 6 weeks into the intervention)
Circulating parathyroid hormone (PTH) concentration
Circulating concentration of parathyroid hormone
Time frame: Pre-intervention; during the intervention (at 3 and 6 weeks into the intervention)
Anion gap
Anion gap from comprehensive metabolic panel
Time frame: Pre-intervention; during the intervention (at 3 and 6 weeks into the intervention)
Insulin
Circulating insulin concentration
Time frame: Pre-intervention; during the intervention (at 3 and 6 weeks into the intervention)
Glucagon
Circulating glucagon concentration
Time frame: Pre-intervention; during the intervention (at 3 and 6 weeks into the intervention)
IGF-1
Circulating IGF-1 concentration
Time frame: Pre-intervention; during the intervention (at 3 and 6 weeks into the intervention)
Beta-hydroxybutyrate
Circulating beta-hydroxybutyrate concentration
Time frame: Pre-intervention; during the intervention (at 3 and 6 weeks into the intervention)
Blood lipids
Total Cholesterol, Triglycerides, HDL Cholesterol, LDL-Cholesterol, Non-HDL Cholesterol
Time frame: Pre-intervention; during the intervention (at 3 and 6 weeks into the intervention)
Cystatin C
Serum cystatin C
Time frame: Pre-intervention; during the intervention (at 3 and 6 weeks into the intervention)
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — IPD will be shared upon reasonable request
Supporting information: Study protocol, Sap
This study is completed, as verified in Dec 2025. You cannot join it, but the record below documents what was studied.
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